Acylated glp-1/glp-2 dual agonists

Abstract

A compound having agonist activity at the GLP-1 (glucagon-like-peptide 1) and GLP-2 (glucagon-like peptide 2) receptors, and a pharmaceutical composition containing the compound or a pharmaceutically acceptable salt or solvate thereof in admixture with a pharmaceutically acceptable carrier, an excipient or a vehicle are provided. The compound can be used, inter alia, in the prophylaxis or treatment of intestinal damage and dysfunction, regulation of body weight, and prophylaxis or treatment of metabolic dysfunction.

What is claimed is: 
     
         1 . A dual agonist or pharmaceutically acceptable salt or solvate thereof represented by the formula:
   R 1 —X*—R 2  
   wherein:   R 1  is hydrogen (Hy), C 1-4  alkyl (e.g. methyl), acetyl, formyl, benzoyl or trifluoroacetyl;   R 2  is NH 2  or OH;   X* is a peptide H[Aib]EGSFTSELATILDψQAARDFIAWLIQHKITD;   ψ is an L or D Lys residue whose side chain is conjugated to a substituent of formula Z 1 —Z 2 —;   and Z 1 —Z 2 — is [17-carboxy-heptadecanoyl]-isoGlu.   
     
     
         2 . The dual agonist or pharmaceutically acceptable salt or solvate thereof according to  claim 1 , wherein X* has the sequence: 
       
         
           
                 
                 
               
                     
                   H[Aib]EGSFTSELATILD[K*]QAARDFIAWLIQHKITD; 
                 
             
                
               
            
           
         
         wherein K* indicates an L lysine residue in which the side chain is conjugated to the substituent Z 1 —Z 2 —. 
       
     
     
         3 . The dual agonist or pharmaceutically acceptable salt or solvate thereof according to  claim 2 , which is: 
       
         
           
                 
                 
               
                     
                   Hy-H[Aib]EGSFTSELATILD[K([17-carboxy- 
                 
                     
                     
                 
                     
                   heptadecanoyl]-isoGlu)]QAARDFIAWLIQHKITD-OH. 
                 
             
                
                
                
               
            
           
         
       
     
     
         4 . A pharmaceutical composition comprising the dual agonist or pharmaceutically acceptable salt or solvate thereof according to  claim 1 , in admixture with a pharmaceutically acceptable carrier, an excipient or a vehicle.